Oncothyreon, a biotechnology company, has begun Phase 1/2 trial of PX-866 in combination with vemurafenib (Zelboraf), a kinase inhibitor indicated for the treatment of unresectable or metastatic melanoma with the BRAF V600E mutation.
PX-866 is a small molecule compound designed to inhibit the activity of phosphatidylinositol-3-kinase (PI-3K), a component of a key cell survival signalling pathway.
The company is conducting the Phase 1/2 trial in collaboration with the Melanoma Research Foundation Breakthrough Consortium (MRFBC).
Lynn Schuchter, MRFBC member Abramson Cancer Center of the University of Pennsylvania haematology oncology division chief and melanoma programme leader, said that while vemurafenib has significantly prolonged the lives of patients with BRAF-mutant melanoma, many patients develop resistance.
"Preclinical evidence suggests that the PI-3 kinase pathway may contribute to this resistance and we are therefore excited to begin this study," Schuchter added.
The Phase 1 portion of the trial is designed to evaluate the safety and tolerability of PX-866 in up to 36 patients with any BRAF-mutant cancer, in combination with twice daily oral administration of vemurafenib.
A dose-escalation design will be used to evaluate three dose levels of PX-866 with up to two dose levels of vemurafenib, to find out the maximum tolerated or recommended dose of both PX-866 and vemurafenib to be used in Phase 2.
The Phase 2 portion is designed to compare anti-tumour activity and safety of PX-866 and vemurafenib at recommend doses, with vemurafenib alone administered at the approved dose.
The primary endpoint of the randomised Phase 2 trial, which will enrol 110 patients, is progression-free survival.
Oncothyreon president and CEO Robert Kirkman said the MRFBC has proposed and is performing the study.
"With the initiation of this trial, Oncothyreon is now conducting five Phase 2 trials of PX-866 in six different tumour types, a broad development programme reflecting our enthusiasm for this product candidate," Kirkman added.